Repression of NR4A1 by a chromatin modifier promotes docetaxel resistance in PC-3 human prostate cancer cells
Repression of NR4A1 by a chromatin modifier promotes docetaxel resistance in PC-3 human prostate cancer cells
复制标题
染色质修饰剂抑制 NR4A1 促进 PC-3 人前列腺癌细胞对多西紫杉醇耐药
DOI：
10.1016/j.febslet.2013.06.029
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发表时间：
2013-08-19
期刊：
影响因子：
3.5
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Yu, Liang;Su, Yan-sheng;Li, Wei
表观遗传沉默机制在人类癌症的化疗耐药性中起重要作用。在这里，我们报告的上调表达的转移相关蛋白1（MTA 1），一个组成部分的核小体重塑脱乙酰化（NuRD）复合物，在化疗耐药的前列腺癌（PCa）。在PC-3细胞中敲低MTA 1抑制细胞增殖并增强多西他赛（DTX）诱导的细胞死亡。相反，MTA 1的过表达促进PC-3细胞中的DTX化学抗性。MTA 1通过与组蛋白去乙酰化酶2（HDAC 2）相互作用，作为核受体NR 4A 1转录的有效辅阻遏物。这些结果表明，MTA 1可能作为一种新的DTX耐药启动PC-3细胞。(C)2013年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Epigenetic silencing mechanisms play an important role in chemoresistance of human cancer. Here we report the upregulated expression of metastasis-associated protein 1 (MTA1), a component of the nucleosome remodeling deacetylation (NuRD) complex, in chemoresistant prostate cancer (PCa). MTA1 knockdown in PC-3 cells inhibited cell proliferation and enhanced docetaxel (DTX)-induced cell death. Conversely, overexpression of MTA1 promotes DTX chemoresistance in PC-3 cells. MTA1 acted as a potent corepressor of the nuclear receptor NR4A1 transcription by interacting with histone deacetylase 2 (HDAC2). These findings suggest that MTA1 may serve as a novel DTX-resistance promoter in PC-3 cells. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.